This invention relates to novel indolylacetylamino acids and derivatives thereof and to processes for their production and use.
It is known that substituted 3-indolylacetic acids, for example, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid (indomethacin), have good anit-inflammatory properties. Such compounds have, however, the known disadvantage of having a low therapeutic index. Even low dosages cause lesions in the stomach epithelium or stomach ulcers (Mathies, Med. Klinik 60, 1863-1869 (1965); Bhargava, K. P., Europ. J. Pharmacol. 22, 191-195 (1973); Green, D., P. G. Goode, and A. B. Wilson, 1969 Fourth International Congress on Pharmacology, Basel, Switzerland, p. 104; Somegyi, A., K. Kovacs, and H. Selye, J. Pharma. Pharmacol. 21, 122 (1969)).
U.S. Pat. No. 3,336,194 describes secondary and tertiary amides of the corresponding 3-indolylacetic acids which, however, have been proved to be less effective than indomethacin according to our own test findings. Japanese Patent 47-44,221 describes the methionine derivative of indomethacin which, however, also is less effective than indomethacin.
It is an objective of the present invention to provide novel compounds which have the effectiveness of indomethacin, which are better tolerated by the stomach and which have lower toxicity. Other objects will be apparent to those skilled in the art.